October 18, 2023 - The New England Journal of Medicine (NEJM) published positive results from the Astellas-and Pfizer-led Phase 3 EMBARK trial of XTANDI® (enzalutamide) plus leuprolide in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR). Patients in the trial were randomized across three study arms: XTANDI plus leuprolide [n=355], placebo plus leuprolide [n=358], or XTANDI monotherapy [n=355]). Results of EMBARK, which met its primary endpoint of metastasis-free survival (MFS), were previously presented at the 2023 American Urological Association Annual Meeting.

Ahsan Arozullah, M.D., MPH, Senior Vice President and Head of Development Therapeutic Areas, Astellas
“In patients with prostate cancer, a rising prostate specific antigen (PSA) level is prognostic of disease growth and an increased likelihood of cancer-related morbidity and mortality. Men who have a PSA level that doubles fast within a short period of time tend to be at higher risk of disease progression and metastasis. The faster the PSA level doubles, the more aggressive the cancer. Despite significant progress in prostate cancer research, in those circumstances additional treatment options that are tolerable and extend metastasis-free survival are still needed.

While XTANDI is already an established standard of care in advanced prostate cancer, the EMBARK trial aimed to understand XTANDI could provide positive patient outcomes in nmHSPC, earlier in the course of the disease – before metastasizing or becoming castration-resistant. Findings demonstrated that the combination of XTANDI plus ADT offers improvements over ADT alone, which is currently used routinely in nmHSPC with high-risk BCR. EMBARK is the first Phase 3 trial to compare outcomes between androgen deprivation therapy (ADT) and a novel hormone therapy (NHT; enzalutamide in combination with ADT or enzalutamide alone) in this patient population to help understand the contribution of each agent to the efficacy and safety of the NHT and ADT combination.

Today’s NEJM publication of EMBARK demonstrates the significance of these potentially practice-changing results for the prostate cancer community. We would like to thank the EMBARK study authors, investigators, patients and their families, and the many others involved for contributing to this research. We look forward to sharing more data from our ongoing clinical development program and to making XTANDI available in this additional indication as quickly as possible, pending regulatory decisions.”

XTANDI, either in combination with leuprolide or as a monotherapy, has not been approved by any regulatory agency for the treatment of patients with nmHSPC with high-risk BCR.

The Astellas-and Pfizer-led Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR) at sites in the United States, Canada, Europe, South America and the Asia-Pacific region. Patients who were considered to experience high-risk BCR had a prostate-specific antigen doubling time (PSA-DT) ≤ 9 months; serum testosterone ≥ 150 ng/dL (5.2 nmol/L); and screening PSA by the central laboratory ≥ 1 ng/mL if they had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer, or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide (n=355), enzalutamide 160 mg as a monotherapy (n=355), or placebo plus leuprolide (n=358). Leuprolide 22.5 mg was administered every 12 weeks.

The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide versus placebo plus leuprolide. MFS is defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death. For more information on the EMBARK trial (NCT02319837) go to www.clinicaltrials.gov.

About Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence
In non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC), no evidence of the cancer spreading to distant parts of the body (metastases) is detectable with conventional radiological methods (CT/MRI), and the cancer still responds to medical or surgical treatment designed to lower testosterone levels.1,2 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a biochemical recurrence (BCR) within 10 years.3 About 9 out of 10 men with high-risk BCR will develop metastatic disease, and 1 in 3 will die as a result of the recurrence.4 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC and high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a prostate-specific antigen doubling time (PSA-DT) ≤ 9 months. High-risk BCR patients with a PSA-DT of ≤ 9 months have a higher risk of metastases and death.5

About XTANDI® (enzalutamide)
XTANDI® (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), and non-metastatic castration-resistant prostate cancer (nmCRPC). XTANDI is currently approved for one or more of these indications in more than 100 countries, including in the United States, European Union, and Japan. Over one million patients have been treated with XTANDI globally.6

U.S. Important Safety Information
XTANDI (enzalutamide) is indicated in the U.S. for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC).

For Important Safety Information for XTANDI in the U.S., please see the Full Prescribing Information.

About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.

About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a commercial agreement to jointly develop and commercialize XTANDI® (enzalutamide) in the United States, while Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing the product outside the United States. Pfizer receives alliance revenues as a share of U.S. profits and receives royalties on sales outside the U.S.

Astellas Forward-Looking Statement
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management’s current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas’ intellectual property rights by third parties.

Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

1 Cancer.net. Prostate Cancer: Types of Treatment (12-2022). https://www.cancer.net/cancer-types/prostate-cancer/types-treatment. Accessed 18 October, 2023.
2 American Society of Clinical Oncology. ASCO Answers: Prostate Cancer (2021). http://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf. Accessed 18 October, 2023.
3 Ward JF, Moul JW. Rising prostate-specific antigen after primary prostate cancer therapy. Nat Clin Pract Urol. 2005 Apr;2(4):174-82. doi: 10.1038/ncpuro0145. PMID: 16474760.
4 Antonarakis, Emmanuel S et al. “The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up.” BJU international vol. 109,1 (2012): 32-9. doi:10.1111/j.1464-410X.2011.10422.
5 Paller, Channing J et al. “Management of patients with biochemical recurrence after local therapy for prostate cancer.” Hematology/oncology clinics of North America vol. 27,6 (2013): 1205-19, viii. doi:10.1016/j.hoc.2013.08.005.
6 Astellas. Data on File. XTANDI patient. January 2023.

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